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Rheumatoid Arthritis: Early Aggressive Treatment Needed

A wealth of research supports early aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) as the best course for preventing joint damage and avoiding the// fate of a wheelchair. Still, the use of DMARDs, even the widely prescribed and generally safe methotrexate, brings the risk of liver damage and other serious complications.

Rheumatoid Arthritis (RA) is a painful and potentially disabling autoimmune disease, which is marked by chronic inflammation of the joints and tissue.

Among those who seek out a doctor's help for joint pain and stiffness, the most common diagnosis is undifferentiated arthritis (UA), or arthritic symptoms that do not add up to a specific arthritic disease. Spontaneous remission occurs in 40 to 50 percent of UA sufferers, while about one-third develop RA. Physicians often face the tough choice of whether to initiate DMARD therapy immediately or to wait and see.

To guide individual treatment decisions, researchers with the Early Arthritis Clinic at Leiden University Medical Center, The Netherlands, have found a formula to help determine whether patients who present with UA are likely to progress to RA. The February 2007 issue of Arthritis & Rheumatism (
/journal/arthritis) features their simple, reliable prediction rule for disease outcome.

Starting with clinical data for over 1,700 arthritis patients, the Leiden team identified 570 patients with recent-onset UA and monitored their disease for one year. At the culmination of follow-up, 177 of the original UA patients fulfilled the diagnostic criteria for RA and 150 had achieved remission; the remaining 94 had been diagnosed with another rheumatologic disease.

Through a combination of questionnaires, physical examination, and blood samples, the team identified 9 clinical variables with independent predictive value for RA: sex, age, localization of symptoms, morning stiffness, the tender joint count, the swollen joint count, the C-reactive protein level, rheumatoid factor positivity, and the presence of anti-cyclic citrullinated peptide antibodies. Then, using the area under the curve (AUC), the diagnostic performance of the prediction rule was evaluated.

A prediction score, ranging from 0 to 14, was calculated for every patient in the group, with a higher score indicating a greater risk of developing RA. None of the patients who had a prediction score of less than 3 progressed to RA during the yearlong observation. In contrast, all of the patients who had a prediction score of 11 or greater did experience progression to RA. Among the patients with scores between 4 and 10 who experienced progression to RA, the frequency of such progression increased with rising scores.

The percentage of patients in whom RA developed was also assessed according to several cutoff values of the prediction score. For example, when the scores 5.0 and 9.0 were chosen as cutoff values, 97 percent of patients with UA who had a score equal to or less than 5.0 did not develop RA, and a score of equal to or greater than 9.0 was associated with progression to RA in 84 percent of the patients.

"Because the prediction rule is accurate and can be easily determined in daily clinical practice, the present model is an important step forward in achieving individualized treatment in patients with recent-onset UA," notes team spokesperson Dr. Tom W. J. Huizinga. "Although the validation cohort is relatively small and the current prediction rule should be evaluated in other early-arthritis cohorts, we believe that the current model allows physicians and patients to make an evidence-based choice regarding whether or not to initiate DMARDs, in the majority of patients presenting with UA."


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